ES2452916T3 - Vicenin 2 and derivatives thereof to use as an antispasmodic and / or prokinetic agent - Google Patents

Abstract

Composition comprising vicenin 2 as an antispasmodic and / or prokinetic agent for use in i) preventing or improving irritable bowel syndrome (IBS), ii) having a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia (FD) , iii) reduce or balance digestive disorders, iv) reduce swelling, v) improve diarrhea or vi) reduce visceral hypersensitivity and / or abdominal pain.

Description

Vicenin 2 and derivatives thereof to use as an antispasmodic and / or prokinetic agent

Technical field

[0001] The present invention relates to a food, a dietary supplement or a pharmaceutical composition comprising vicenin 2 for use in obtaining beneficial effects for the intestine. In particular, the present invention relates to a composition comprising vicenin 2 as an antispasmodic and / or prokinetic agent for use in i) preventing or improving irritable bowel syndrome (IBS), ii) having a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia (FD), iii) reduce or balance digestive disorders, iv) reduce swelling, v) improve diarrhea or vi) reduce visceral hypersensitivity and / or abdominal pain, and the use of Composition comprises Vicenin 2 to maintain a healthy bowel, maintain normal digestion, improve bowel regularity, aid in healthy bowel mobility, bowel movement and / or a frequency of bowel movements, consistency and / or shape of healthy bowel movements and / or improve bowel function and / or induce antispasmodic and / or prokinetic activity.

Background of the invention

[0002] Maintaining optimal digestive health is particularly important for vitality and well-being at all stages of life. The effectiveness of the digestive tract of each person can be very relevant in daily energy and general health. Almost everyone suffers gastrointestinal discomfort that affects the quality of life.

[0003] Symptoms may be impaired swelling, mobility and intestinal transit, as well as abdominal pain. Many times these symptoms are combined with a bad mood, lack of concentration and energy and can consequently prevent people from sleeping, working, exercising and socializing with friends.

[0004] Gastrointestinal disturbances are triggered mainly by contractions of the ileum, which may be caused by several factors. For example, daily stress, sensitivity and food allergies, infections, genetic predisposition, altered intestinal flora or deregulation of brain-intestine interference can lead to the development of gastrointestinal disorders, dyspepsia or irritations of the type of irritable bowel syndrome. (IBS) or inflammatory bowel disease (IBD).

[0005] Induction of digestive relief includes the regulation of transit through the gastrointestinal tract and the relief of pain associated with digestion, as well as aiding in reducing the causes that lead to gastrointestinal discomfort.

[0006] Gastrointestinal disorders are divided into structural and functional disorders. Structural diseases, for example, hemorrhoids, types of colitis, such as Crohn's disease or C. ulcerosa, as well as colon cancer, can be identified by pathologists and, sometimes, cured by medical technology. Non-structural functional gastrointestinal disorders, such as functional dyspepsia (FD) or IBS, are less susceptible to treatment with explanation or effective treatment. On the one hand, doctors usually look for structural evidence for diagnostic purposes and, on the other hand, patients are reluctant to speak clearly about their intestines and their malfunction. This leads to the situation that functional gastrointestinal disorders are often not diagnosed or treated correctly. Ref: 2.5.

[0007] More recent scientific studies relate the mind and body as part of a system in which their deregulation can cause discomfort and disease. In the first years of life, genetics, in addition to environmental factors, such as family influences in the expression of disease, abuse, major losses or exposure to infections, can affect psychosocial development in terms of a person's susceptibility to life stress or psychological status and coping skills, as well as susceptibility to abnormal motility-dysfunction of the intestines, immunity of the altered mucosa or visceral hypersensitivity. In addition, these “brain-intestine” variables influence their expression reciprocally. Therefore, functional gastrointestinal disorders are a product of this interaction of psychosocial factors and altered physiology of the intestines through the brain-intestine axis. Ref: 5.

[0008] Current drug development is directed to neuropeptides and receptors present in the enteric system and the CNS to treat the stress-mediated effects of bowel CNS modulation. Under development are drugs that recognize serotonin, encephalin and opioid agonist, substance P, polypeptide related to the calcitonin gene, cholecystokinin, neuroquinine receptor and corticotrophin-releasing hormone antagonists, etc.

[0009] New drugs for IBS-d that recognize the neurotransmitter serotonin and its receptors have been approved. Due to the serious side effects, they have only been approved with a significant limitation only for women and severe IBD, who have not responded to conventional therapy. Ref. 3.5.

[0010] It is estimated that 10 to 20% of the total world population is affected by IBS. It is estimated that among all those affected with IBS, 60% are women and 40% are men. It is also believed that approximately 70% of those affected with IBS do not seek medical help. IBS is a common problem, but most people affected are not aware of the problem or tend to avoid it and not discuss it with their doctor.

[0011] Thus, it is important to develop ingredients for functional foods and dietary supplements, in addition to developing drugs.

[0012] The entire length of the intestine is controlled by the nervous system, which returns transports and returns signals between the intestine and the brain, controlling factors, such as how quickly food is pushed through the intestines. The understanding of these basic neuroenteric mechanisms and the brain-intestine axis demonstrated the need for an agent that improves gastrointestinal irritations at the neurotropic and musculotropic levels.

[0013] Despite considerable efforts by academic researchers and the pharmaceutical and food industry, the development of new ingredients to prevent, reduce or treat functional gastrointestinal disorders or to reduce their symptoms has been slow and did not lead to innovations.

[0014] The aim of the present invention was to provide new active ingredients for preventing and improving discomfort and functional gastrointestinal diseases, such as IBS, suitable as functional foods, dietary supplement ingredients and drugs.

Summary Description of the Invention

[0015] The present inventors have surprisingly found that a composition comprising the active substance vicenin 2 has antispasmodic activity that inhibits neurotropic and musculotropic levels, as well as prokinetic activity, both acting in the reversible inhibition of cholinesterase and acetylcholine agonist.

[0016] Thus, the present invention describes a new antispasmodic and / or prokinetic agent, which helps prevent and improve bowel health, such as gastrointestinal discomfort, functional dyspepsia (FD) or irritable bowel syndrome ( IBS).

[0017] The present invention relates to a composition comprising vicenin 2 as an antispasmodic and / or prokinetic agent for use in i) preventing or improving irritable bowel syndrome (IBS), ii) having a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia (FD), iii) reduce or balance digestive disorders, iv) reduce swelling, v) improve diarrhea or vi) reduce visceral hypersensitivity and / or abdominal pain, and the use of Composition comprises Vicenin 2 to maintain a healthy bowel, maintain normal digestion, improve bowel regularity, aid in healthy bowel mobility, bowel movement and / or a frequency of bowel movements, consistency and / or shape of healthy bowel movements and / or improve bowel function and / or induce antispasmodic and / or prokinetic activity. This ingredient is preferably an ingredient derived from a plant.

[0018] For example purposes, it is described herein that a functionally active derivative of vicenin 2 can be used for the conditions mentioned above.

[0019] In particular, the present invention relates to a composition comprising as active ingredient vicenin 2 for use in improving the health of the intestines.

[0020] In addition, the present invention relates, in particular, to a composition comprising as active ingredient vicenin 2 for use as an antispasmodic and / or prokinetic agent. Preferably, the composition comprises or derives from a plant preparation comprising the active ingredient and, more preferably, the plant preparation has been enriched with the active ingredient.

[0021] The plant preparation is preferably selected from a group consisting of Perilla, Urtica, Passiflora, Camellia, Cayaponia, Colocasia, Desmodium, Hordeum, Origanum, Ocimum, Jatropha, Parkinsonia, Peperomia, Piheranthos, Centaurea, Indigo, Bomb , Lychnophera, Asplenium, Chinotto, Citrus, Viola, Trigonella, rosemary, mint, thyme, basil, sage, oregano, lavender and other species that belong to Lamiaceae, Labiatae and Urticaceae, Rosales or Malpighiales and can be a preparation of leaves, a fruit preparation, a seed preparation, a stem preparation, a flower preparation, a cocoon preparation, a root preparation or a mixture of different parts of the plant. Most preferably, the preparation is a preparation of leaves or a preparation of part of the plant areas.

[0022] In a more preferred embodiment, the active ingredient is an isolated vicenin 2 obtained by isolation or chemical synthesis.

[0023] In addition, the present invention relates to the use of vicenin 2 to maintain a healthy bowel, prevent or improve irritable bowel syndrome (IBS), have a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia. (FD), maintain normal digestion, reduce or balance digestive disorders, improve intestinal regularity, support healthy bowel movement, bowel movement and / or frequency, consistency and / or healthy bowel movements, reduce swelling , improve bowel function, such as improved constipation, improve diarrhea, reduce visceral hypersensitivity, abdominal pain and / or induce antispasmodic and / or prokinetic effects.

[0024] In particular, the present invention relates to vicenin 2 for use in maintaining a healthy intestine, preventing

or improve irritable bowel syndrome (IBS), have a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia (FD), maintain normal digestion, reduce or balance digestive disorders, improve intestinal regularity, support a healthy bowel mobility, a bowel movement and / or a frequency, consistency and / or healthy bowel movements, reduce swelling, improve bowel function, such as improving constipation, improve diarrhea, reduce visceral hypersensitivity, abdominal pain and / or induce antispasmodic and / or prokinetic effects.

[0025] In a further embodiment, the present invention is useful in a method of maintaining a healthy bowel, preventing or improving irritable bowel syndrome (IBS), having a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia. (FD), maintain normal digestion, reduce or balance digestive disorders, improve intestinal regularity, support healthy bowel movement, bowel movement and / or frequency, consistency and / or healthy bowel movements, reduce swelling , improve intestinal function, such as the improvement of constipation, improve diarrhea, reduce visceral hypersensitivity, abdominal pain and / or induce antispasmodic and / or prokinetic effects, which comprises administering a composition comprising as active substance vicenin 2.

[0026] For example purposes, a kit is described herein comprising a composition comprising the antispasmodic and / or prokinetic active ingredient vicenin 2 or functionally active derivatives thereof and instructions for administration of said composition.

[0027] Preferably, the composition for use according to the present invention is comprised of a food product, dietary supplement or medicament and the concentration of the active ingredient is 0.1 μg to 500 μg, preferably 2.5 μg to 50 μg and most preferably from 5 μg to 15 μg.

[0028] In a further preferred embodiment, the preparation is a plant extract, most preferably a liquid or powder extract obtained by extraction.

[0029] The composition for use according to the present invention may additionally comprise an additional agent capable in addition to improving intestinal health. This additional agent may preferably be a prebiotic agent, a probiotic agent, a lipid, a loading agent, a medicament, an antispasmodic agent or an anti-inflammatory agent.

[0030] Preferably, the medicament is an additional antispasmodic agent, a tricyclic antidepressant, a cholecystokinin-1 antagonist, a serotonergic agent, a benzodiazepine or analogue, a neurokinin antagonist, a guanylate cyclase C agonist, a channel activator C1-C2, a Cl secretion blocker, a GLP1 analogue, an κ-opioid agonist, an antacid, a sodium phosphate, an NA reuptake inhibitor, omeprazole analogue, glucocorticoid or an antibiotic.

[0031] In addition, for example purposes, a production process of a preparation of the active ingredient as defined above, which comprises the steps of: a) the selection of the vegetable raw material, b) the preparation of the vegetable raw material, c) apply an extraction process using solvent extraction and / or filtration techniques, preferably followed by concentration and / or spray drying of the liquid extract in a powder, d) determine the concentration of the active substance and e) select the preparation comprising the active ingredient at a concentration of at least 0.01%.

[0032] In the process mentioned above, the preparation may comprise the active ingredient at a concentration of at least 0.02%, or, at a concentration of at least 0.1%, 0.15%, 0.2% or most preferably at a concentration of at least 0.2%, 0.25% or 0.3%.

In some cases, the preparation may comprise the active ingredient in a concentration of at least 0.2%, more preferably, at a concentration of at least 0.5%, 1.5%, 3 , 0% or most preferably at a concentration of at least 2.0%, 3.0% or 5.0%.

[0034] Detailed descriptions of conventional methods, such as those used herein, can be found in the literature, for example in the book "Industrial Scale Natural Products

Extraction ", published in 2011 by Wiley-VCH.

[0035] The analytical method for determining the concentration of vicenin 2 may be, for example, a chromatographic method called high performance liquid chromatography. High performance liquid chromatography (HPLC) is one of the most popular analytical chemistry techniques. A UV detector is used, detecting at 320 nm. For the determination of the concentration of vicenin 2, a reference of vicenin 2 or its derivatives can be used as reference material. For example, apigenin can be used as a reference substance and the content of vicenin 2 is calculated through the difference in the weight of the molecule and the slope and the intersection of the calibration curve for apigenin.

[0036] In the process, the vegetable raw material may be of the Perilla species, in particular Perilla frutescens Britton crispa variety or Kuta acuta variety. The vegetable raw material can be prepared by drying, cutting and / or grinding. The extraction can preferably be carried out with a raw material whose particle size was reduced to less than 2 mm2. The solvent may be water, methanol, ethanol, propanol, isopropanol, ethyl acetate, hexane, chloroform or dichloromethane. Water is most preferably used, since glycosides, such as vicenin 2, which have hygroscopic properties, are extracted by hot water more efficiently than with alcohol. In addition, some volatile allergenic compounds, such as perilaldehyde, methyleneugenol and myristicin, which may appear in target species containing vicenin 2, can be removed by hot water.

[0037] The ratio of raw material to solvent is preferably between 1: 100 to 20: 100 and more preferably between 2: 100 and 10: 100.

[0038] Extraction can preferably be performed at room temperature up to 150 ° C. Extraction is carried out more preferably from 90 ° C to 125 ° C. In a more preferred embodiment, heat with additional pressure can be used

[0039] The extraction time may be 10 minutes to 2 hours, more preferably 20 minutes to 50 minutes.

[0040] The plant for the process can be selected from the group consisting of Perilla, Urtica, Passiflora, Camellia, Cayaponia, Colocasia, Desmodium, Hordeum, Origanum, Ocimum, Jatropha, Parkinsonia, Peperomia, Piheranthos, Centaurea, Indigo, Bomb, Lychnophera, Asplenium, Chinotto, Citrus, Viola, Trigonella, rosemary, mint, thyme, basil, sage, oregano, lavender and other species belonging to Lamiaceae, Labiatae and Urticaceae, Rosales or Malpighiales.

[0041] The process provides an extract with a higher concentration of the active ingredient than the prior art processes due to the concentration of the active ingredient. Higher concentration is achieved using state-of-the-art extraction equipment, which allows an optimal interaction between the raw material and the extraction solvents. All critical stages of the process, for example temperature, are controlled in the process at any time and continuous adaptations are possible to ensure the highest performance for the active ingredient. Due to the selection of extraction solvents combined with optimized physical conditions, it is possible to reduce unwanted substances that may appear naturally in different raw materials.

[0042] In addition, an active ingredient preparation can be obtained by the process described above. The preparation is used as an antispasmodic and / or prokinetic agent and to maintain a healthy bowel, prevent or improve irritable bowel syndrome (IBS), have a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia (FD), maintain normal digestion, reduce or balance digestive disorders, improve intestinal regularity, support healthy bowel movement, bowel movement and / or frequency, consistency and / or healthy bowel movements, reduce swelling, improve function intestinal, such as improving constipation, improving diarrhea, reducing visceral hypersensitivity, abdominal pain and / or inducing antispasmodic and / or prokinetic effects.

Brief description of the figures:

[0043]

Figure 1: Effect of vicenin 2 on the contraction of the rat ileum. The data is normalized to the maximum effect of acetylcholine (100% control). Average ± SE of 1-15 experiments.

Figure 2: Effect of AUC-V (0.005 mg / ml) on the contraction of the rat ileum induced by increasing concentrations of acetylcholine. The data is normalized to the maximum effect of acetylcholine (100% control). Atropine (5x10-5 mg / ml) was used as a positive control. Average ± SE of 4 independent experiments. The acetylcholine curves modulated by the compound AUC-V and atropine were significantly different from the acetylcholine curve (without additional additions).

Figure 3: Effect of compound AUC-V (0.05 mg / ml) on rat ileum contraction induced by

increasing concentrations of acetylcholine. The data is normalized to the maximum effect of acetylcholine (100% control). Average ± SE of 7-10 independent experiments. The curves induced by AUC-V are significantly different from the acetylcholine curve (without additional additions).

Figure 4: Effect of compound AUC-V (0.005 mg / ml) on the contraction of rat ileum induced by increasing concentrations of barium ion. Paraverin (4x10-2 g / ml) was used as a positive control. The data is normalized to the maximum effect of barium ion (100% control). The curves mediated by the compound AUC-V and papaverine were significantly different from the acetylcholine curve without additions. Average ± SE of 4 independent experiments.

Figure 5: Effect of AUC-V (0.05 mg / ml) on the contraction of the rat ileum induced by increasing concentrations of barium ion. The data is normalized to the maximum effect of barium ion (100% control). The curves induced by AUC-V are significantly different from the acetylcholine curve without additional additions. Average ± SE of 6-9 independent experiments.

Figure 6: Acute effects of vicenin 2 (AUC-V) on cortical network activity in vitro. The changes in the speed of the action potentials for the treatment of 9 accumulated concentrations in the range of 10 pg / ml to 300 μl / ml (average ± standard error, n = 17; paired Student t test: * p are represented) � 0.05; ** p � 0.01; *** p� 0.001).

Detailed description of the invention

[0044] The present inventors surprisingly found an agent that has antispasmodic and prokinetic effects.

[0045] In particular, the inventors found surprisingly that Vicenin 2 exhibits antispasmodic effects to the smooth muscles of the gastrointestinal tract and prokinetic effects that support GI mobility. This efficacy is very beneficial for the health of the intestine, since digestive discomfort and intestinal irritation occur when the muscles in the intestine contract more quickly or more slowly than normal, causing pain, cramping, swelling, diarrhea or constipation. Ref: 4, 5, 6.

[0046] The antipespasmodic effect of vicenin 1 or an extract comprising vicenin 2 maintains a healthy bowel, prevents or improves irritable bowel syndrome (IBS), has a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia ( FD), maintains normal digestion, reduces or balances digestive disorders, improves intestinal regularity, supports healthy bowel movement, bowel movement and / or frequency, consistency and / or healthy bowel movements, reduces swelling, Improves intestinal function, such as improving constipation, improving diarrhea, reducing visceral hypersensitivity, abdominal pain or inducing antispasmodic and / or prokinetic effects.

[0047] Typical symptoms for IBS are hypersensitivity and abdominal pain, bloating, gas, discomfort and altered bowel habits (ie, either constipation (IBS-E), diarrhea (IBS-d) or both (Alternate IBS), which can destroy the quality of life of severely affected people, but do not lead to fatal diseases and do not develop bowel cancer Ref: 4.

[0048] Although the exact cause is highly variable among individuals, there are certain topics that trigger attacks, including stress, infections, altered intestinal flora, sensitivity to food or allergies, irregular meal times or lack of fiber in the diet. In the IBS, the intestine responds with powerful contractions or spasms to stimuli that would not bother other people simply by eating food. The types of IBS and the causes among individuals require a different treatment.

[0049] First-line therapy for all forms of IBS includes education, reconfirmation, exercise, avoiding triggering and dietary modifications. Ref.1 Psychosocial therapies to reduce daily stress and anxiety are important and include counseling or seminars to learn how to optimize cognitive behavior.

[0050] There are several food functions or dietary supplements to support healthy digestion. Current functional food ingredients to maintain a healthy digestion are directed to a healthy microbiological flora (probiotics and prebiotics). These ingredients help reduce flatulence, the feeling of being full, or constipation. In addition, a series of herbal therapies have been announced without evidence to support their benefit, such as peppermint oil and TCM.

[0051] Traditional drug therapies, in general, only target individual symptoms. Osmotic laxatives are prescribed for IBS-c and antidiarrheal agents, such as loperamide, for IBS-d. The pain associated with IBS can be treated with antispasmodics, such as hiosciamine or tricyclic antidepressants, such as amitriptyline. General relief of the multiple symptoms of IBS has rarely been demonstrated with these agents and are often associated with adverse effects, some of which mimic the symptoms of IBC.

[0052] The present invention provides a new important possibility of bowel health therapy that not only addresses the symptoms, but also attacks the problems systemically.

Definitions

[0053] It should be noted that the term "one or" one "entity refers to one or more of that entity; for example, "an antibody" is understood to represent one or more antibodies. Therefore, the terms "a" (or "one"), "one or more", and "at least one" may be used interchangeably herein.

[0054] By an "isolated" ingredient or principle, variant, or derivative thereof, is understood as an agent that is not in its natural environment. No particular level of purification is required. For example, an isolated active substance can be extracted from its native or natural environment. Synthetically produced active ingredients are considered "isolated" for the purpose of the invention, since they are native or synthetic active ingredients that have been separated, fractionated, or partially or substantially purified by any suitable technique.

[0055] Unless otherwise indicated, the terms "disorder" and "disease" are used interchangeably herein.

[0056] By "subject" or "individual" or "animal" or "patient" or "mammal", is meant any subject, particularly a mammalian subject, for example, a human patient, for whom diagnosis, prognosis is desired. prevention

or therapy

[0057] "Maintaining a healthy bowel", according to the present invention, can be understood as maintaining a normal digestion with a bowel movement and a frequency of normal deposition, pain and swelling.

[0058] "Prevention or improvement of functional dyspepsia or irritable syndrome disease", according to the present invention, it can be understood that the active ingredient has beneficial physiological effects to avoid or improve constipation, diarrhea, or both alternated, pain abdominal and visceral hypersensitivity, swelling and discomfort.

[0059] "Improving irritable bowel syndrome" means in this context that it produces a beneficial effect in a functional gastrointestinal disorder with symptoms of hypersensitivity and abdominal pain, swelling, gas, discomfort and altered bowel habits (that is, either constipation ( IBS-c), diarrhea (IBS-d) or both (alternate IBS), which can destroy the quality of life of severely affected people, but do not lead to fatal diseases and do not develop bowel cancer Ref: 4.

[0060] "Inducing antispasmodic effects" can be defined as the modulation of the cholinergic system, so that muscle spasms are suppressed. According to the present invention, the stimulation of cholinergic neurons is reduced which results in the relaxation of intestinal smooth muscle. Preferably, the modulation of a musculotropic local antispasmodic effect is found within the muscles of the intestine.

[0061] It was shown that the antispasmodic activity of the active ingredient of the invention was local in the ileum, muscolotrope, to counteract the triggers, such as food or additives. In addition, a neurotropic activity was confirmed that indicated that a spasmolytic effect resulting from stress, communicated through the brain-intestine connection, can be positively modulated. This concept is new and there was a gap in prevention and improvement that could be closed with the active substance of the invention and the efficacy investigated.

[0062] "Antispasmodic activity", according to the present invention, can be defined as an activity that suppresses muscle spasms, in particular for contractions of smooth muscles, especially in tubular organs of the gastrointestinal tract.

[0063] "Prokinetic activity", according to the present invention, can be defined as the improvement of gastrointestinal mobility by increasing the frequency of bowel contractions, but without altering its rhythm.

[0064] Vicenin 2 is a flavonoid that has a series of derivatizations. Vicenin 2 or its synonyms Apigenin-6,8-diC-glycoside, 5,7,4'-Trihydroxiflavone-6,8-di-C-glucoside, 5,7-Dihydroxy-2- (4-hydroxyphenyl) -6, 8-bis [(2S, 3R, 4R, 5S, 6R) 3,4,5-trihydroxy-6 (hydroxymethyl) oxan-2-yl] chromen-4-one with CAS registration number 23666-13-9 is a flavonoid found in a set of plant species. Vicenin 2 can be found, among others, in Perilla species, Urtica species, Passiflora species, Camellia species, Cayaponia species, Colocasia species, Desmodium species, Hordeum species, Origanum species, Ocimum species, Jatropha species, Parkinsonia species, Peperomia species, Piheranthos species, Centaurea species, Indigo species, Bomba species, Lychnophera species, Asplenium species, Chinotto species, Citrus species, Viola species, species of Trigonella, species that belong to Lamiacea, Labiatae and, for example, rosemary, mint, thyme, basil, sage, oregano, lavender and species that belong to Lamiaceae, Labiatae and Urticaceae, Rosales or Malpighiales.

[0065] The standard process for purifying vicenin 2 outside the plant material is based on different chromatographic methods known to the person skilled in the art and, consequently, vicenin 2 can be identified by spectroscopy. These processes can be reviewed in several publications. Ref. 15, 16

[0066] So far the literature describes that vicenin 2 has anti-cancer, anti-inflammatory and antinociceptive effects. Ref. 7, 8, 9, 10, 11 "A plant extract comprising vicenin 2 or a functionally active derivative thereof 'means here, according to the present invention, an extract comprising vicenin 2 at a concentration that can be measured. plant extract or preparation preferably comprises the active ingredient preferably at a concentration of 0.02% to 0.3%, more preferably 0.1% to 0.2%, and most preferably 0.15% to 0.2 %.

[0067] In some cases, the preparation may comprise the active ingredient at a concentration of at least 0.2%, more preferably, at a concentration of at least 0.5%, 1.5%, 3, 0% or most preferably at a concentration of at least 2.0%, 3.0% or 5.0%.

[0068] As used herein, "functionally active derivatives" or "functionally active analogs", which are used interchangeably herein, vicenin 2 refers to compounds structurally similar to vicenin 2, for example, flavone c-glycosides or flavone o-glycosides, in particular, apigenin 7-O-�-glucuronide, apigenin-7-O- [�-glucuronosyl (1-2 �-glucuronide], luteolin 7-O- [�-glucuronosyl ( 1-2) �glucuronide], luteolin 7-O-�-glucuronide or escutelarein O-�-glucuronide (escutelarin), which also show antispasmodic and / or prokinetic activity. Antispasmodic and / or prokinetic activity can be measured as shown in the examples There are several possibilities to investigate the antispasmodic and / or prokinetic activity that are known to the person skilled in the art.In vitro studies, such as receptor binding assays or enzymatic inhibition studies, are standard methods for identifying ficating the activity and its mode of action In addition, ex vivo studies are used to confirm efficacy in the target area, for example, as shown in example 1, in which the antispasmodic effect in isolated rat intestines was investigated . In addition, in studies of animals in vivo and humans in vivo, they are used to confirm the effect on the biological system. Measurements to quantify antispasmodic and prokinetic activity in in vivo studies that target gastrointestinal mobility are, for example, the frequency of bowel movements and the consistency of bowel movements. These types of studies are known to the person skilled in the art.

[0069] "The active ingredient", as used herein, refers to an ingredient or principle having antispasmodic and / or prokinetic activity, preferably, vicenin 2 or a functionally active derivative or analog thereof.

[0070] For the purpose of inducing antispasmodic and / or prokinetic effects, the concentration of the active ingredient in the composition is 0.1 μg to 500 μg, preferably 2.5 μg to 50 μg and, most preferably, 5 μg to 15 μg of vicenin 2.

[0071] The composition is a vegetable preparation or plant extract, most preferably a liquid or powder extract obtained by extraction and comprising vicenin 2.

[0072] The composition according to the present invention may be comprised in a functional food product, dietary supplement or in a drug. "A functional food product", according to the present invention is understood to be a food product, beverage or infant formula, which offers, in addition to a nutritional value, a health benefit, which supports and improves health and well-being or It helps reduce the risk of developing a disease.

[0073] "A dietary supplement product", according to the present invention are food products in the form of a tablet, tablet, capsule, powder or liquid, which is intended to be taken by mouth, and contain substances, such as vitamins, minerals, foods, Vegetable agents, amino acids and aims to complement the usual intake of these substances through the normal diet.

[0074] "A medicament / drug / medicine", according to the present invention, is any substance with the potential to prevent or cure a disease or improve physical or mental well-being. If not indicated otherwise, the terms "drug", "medicine" or "medicine" are used interchangeably in this document and shall include, but not limited to, all (A) items, medicines and preparations for internal or external use, as well as any substance or mixture of substances intended to be used for the diagnosis, cure, mitigation, treatment or prevention of a disease of man or other animals; and (B) articles, medicines and preparations (except food) whose purpose is to affect the structure or any function of the body of man or other animals; and (C) the articles intended to be used as a component of any article specified in clauses (A) and (B). The term "drug", "medicine" or "medicine" shall include the complete formula of the preparation intended for use in man or other animals that contain one or more "agents", "ingredients", "compounds", "substances" or "(chemical) compositions" and, in some other context, also other pharmaceutically inactive excipients, such as fillers, disintegrants, lubricants, glidants, binders to ensure easy transport, disintegration, disaggregation, dissolution and biological availability of the "drug", "medicine", or "medicine" in one place

desired target within the body of man or other animals, for example, on the skin, in the stomach or intestine. The terms "agent", "compound" or "substance" are used interchangeably herein and should include, in a more particular context, but without limitation, all pharmacologically active agents, that is, agents that induce a biological effect or desired pharmacological or are investigated or analyzed for the ability to induce said possible pharmacological effect by the methods of the present invention.

[0075] As used herein, the terms "treat" or "treatment" refer to both therapeutic treatment and prophylactic or preventive measures, in which the objective is to prevent or slow down (decrease) a physiological change or disorder. unwanted, such as the development of an intestinal disease. Beneficial or desired clinical outcomes include, but are not limited to, the relief of symptoms, the decrease in the extent of the disease, the stabilization (i.e., no worsening) of the disease status, the delay or slowdown of the progression of disease, improvement or palliation of disease status, and remission (partial

or total), either detectable or undetectable. Those who need treatment include those who already have the condition or disorder, as well as those likely to have the condition or disorder, or those in whom the manifestation of the condition or disorder should be prevented.

[0076] These and other embodiments are described and encompassed by the description and examples of the present invention. Public libraries and databases can be extracted using, for example, electronic devices, additional bibliography referring to any of the materials, methods, uses and compounds to be used according to the present invention. For example, the public database "Medline" or "Pubmed" can be used, which is produced by the National Center for Biotechnology Information and / or the National Library of Medicine at the National Institutes of Health. More databases and web addresses, such as the "Martindale’s center" virtual library, are known to the person skilled in the art and can also be obtained using internet search engines.

[0077] Several documents are cited throughout the text of this report.

[0078] The above description describes, in general, the present invention. A more complete understanding can be obtained by reference to the following specific examples.

EXAMPLES

[0079] The following examples further illustrate the invention, but should not be construed to limit the scope of the invention in any case.

[0080] The practice of the present invention will use, unless otherwise indicated, conventional techniques of plant biology, chemistry, biochemistry, physiology and pharmacology that are among the usual techniques of the sector.

Example 1: Vicenin 2 has antispasmodic activity

Methods and compound

[0081] An isolated vicenin 2 compound was analyzed for its antispasmodic effect with respect to the cholinergic system and with respect to the non-specific concentration mediated by Ba ++. Therefore, the rat ileum was pre-contracted with increasing concentrations of acetylcholine or Ba ++. The displacement of any of the concentration response curve by the compound was determined. As positive controls, atropine or papaverine were used depending on the type of experiment. The isolated vicenin 2 showed good solubility.

Calculation of the concentrations to be used in the experiments:

[0082] The dose of vicenin 2 for humans was estimated to be between 5 and 15 μg / 70 kg body weight corresponding to 0.071 and 0.214 μg / kg body weight. Due to the higher metabolism in rodents compared to humans, the doses were estimated to be approximately 0.5 to 1.49 μg / kg body weight. The central compartment (hydrophilic extracts) (blood) is approximately 7% of the total body volume, that is, between 0.5 / 70 g and 1.4 μg / 70 g of blood. Since the blood is in direct contact with the ileum, a concentration of 7 to 20.86 μg / kg (0.007 to 0.021 μg / g) is expected for the ileum. Note: the calculations were not corrected for a specific gravity (density) of liquids (possibly differing by exactly 1.0) and for absorption (which was assumed to be 100%; no data available). Therefore, it was reasonable to transfer these calculations in vivo to the in vitro experiments and in these experiments 10 and 100 µl of a stock solution was used per 10 ml of incubation bath. Therefore, the final concentrations of AUC-V were 0.005 or 0.05 mg / ml bath volume.

[0083] Acetylcholine sulfate and barium chloride were from Roth, Karlsruhe, Germany, and Sigma-Aldrich Chemie, Deisenhofen, Germany. All other reagents and compounds used for incubations were obtained from Roth, Karlsruhe, Germany.

Rat ileum

[0084] Under the protocol approved by the Animal Care and Use Committee of Münster, Germany, male and female rats (Charles River, Sulzfeld, Germany) weighing 200 to 320 g were used. The rats were anesthetized (CO2). The nearby ileum was removed, washed and placed in a Krebs-Henseleit solution. 1 cm segments were placed in 10 ml organ baths with a resting tension of 1.0 g (preload). One end was attached to a force displacement transducer (lever transducer B40, Typ 373) combined with a two-channel amplifier (type 301, Hugo Sachs Elektronik, March, Germany); a multi-pen recording device (Rikadenki Kogyo, Tokyo, Japan) was used. The composition of the Krebs-Henseleit solution was (mM): NaCl 118.1, KCl 4.7, CaCl2 2.5, MgSO4 1.2, NaHCO3 25 and glucose 5.6. The solution was maintained at 37 ° C, p 7.4 and was gassed with carcinogen (a mixture of 95% O2 / 5% CO2). The equilibration time for the ileum before starting the experiment was at least 30 minutes. After treating the tissues with the extracts for 3 minutes, the response curves to the accumulated concentration using acetylcholine or barium ion were recorded isotonic in the organ bath and the effect was allowed to reach a steady state at each concentration.

[0085] The results were normalized to 100% (maximum effect of acetylcholine or barium ion alone).

Statistic analysis

[0086] Differences between complete curves were obtained by comparing the F values of the best fit curves using GraphPad-Prism (version 3.00, GraphPad Software, Inc., 1999). P <0.05 was considered statistically significant.

Results

[0087] As shown in Figure 1, Vicenin 2 induced a slight (not significant) relaxation on its own. Data are shown as% of the maximum effect of acetylcholine (controls in the presence of 10 μg / ml). This means that it lacks a direct spasmolytic effect.

[0088] The effect of various concentrations of acetylcholine and the interaction with vicenin 2 are shown below (Figure 2). Low concentrations of the compound (0.005 mg / ml) shifted the acetylcholine curve to the right in a competitive manner. The data indicate a neurotropic antispasmodic effect. Atropine (positive control) shows the expected competitive neurotropic antispasmodic effect, which indicates that the basis of the experiment works. The use of atropine is mimicked by the commercialized N-butylscopolamine (Buscopan®).

[0089] These experiments were repeated while the concentration of vicenin 2 was increased 10 times, from 0.005 to 0.05 mg / ml (final bath concentration). The data is shown in Figure 3. The increase in compound concentrations results in a more intense right and down shift of the acetylcholine curve, which indicates a concentration dependent effect.

[0090] The effect of various concentrations of Ba ++ and the interaction with vicenin 2 are shown below (Figure 2). Low concentrations of the compound (0.005 mg / ml) shifted the Ba ++ curve down, indicating a non-competitive antispasmodic effect. The data indicate a musculotropic antispasmodic effect. Papaverine (positive control) shows the expected noncompetitive musculo-tropic antispasmodic effect, which indicates that the basis of the experiment is correct and works.

[0091] These experiments were repeated while the concentration of the compound was increased 10 times, from 0.005 to 0.05 mg / ml (final bath concentration). The data is shown in Figure 5. The compound shows additional results in a shift to the right and down of the Ba ++ curve, which indicates a non-competitive inhibition (antispasmodic effect) of the Ba ++ effect. The effects were as intense as at lower concentrations shown in Figure 5.

Discussion

[0092] Extracts and drugs have been analyzed in two ways: first, if they had an effect on their own (called spasmolytic effect), and secondly, if they have an antispasmodic effect against compounds that induce the concentration of smooth muscle .

[0093] The antispasmodic effect on smooth muscles that lead to relief of gastrointestinal symptoms that include the symptoms of bowel disease can be achieved by two types of effective compounds: they must have neurotropic or musculotropic spasmodic effects or even both. Physiologically, a neurotropic effect is mediated through acetylcholine; A musculotropic effect is mediated through, for example, toxic compounds. Surprisingly, the compound vicenin 2 has an antispasmodic activity, inhibiting neurotropic and musculotropic activity. What is important, its effects

show a dependence on the concentration with respect to its antispasmodic activity. Its effects are not as strong as the typical series head compounds (positive controls): in this case, the effects were minor compared to atropine (experiments with acetylcholine) or papaverine (experiments with Ba ++).

[0094] In summary, the compound vicenin 2 has spasmodic effects using two different mechanisms of action that probably help when there is an irregular contraction that leads to GI symptoms. This effect was surprising, as other flavonoid glycosides have been described that have weaker effects.

Example 2: Vicenin 2 has prokinetic activity

Methods and compounds

[0095] The objective of this example was the evaluation of the acute neuroactive effects of vicenin 2 (called AUC-V) on the neuronal activity of the murine frontal cortex networks in vitro using multichannel electrophysiological records.

[0096] Therefore, in a first stage, the dose-effect curve of vicenin 2 was represented by the cumulative increase in the concentration of the substance, so that the spectrum of activity of the substance is optimally covered with 9 concentrations. Concentrations of 100 fg / ml, 10 pg / ml, 100 pg / ml, 1 ng / ml, 100 ng / ml, 1 μg / ml, 10 μg / ml, 100 μg / ml and 300 μg / ml were used.

[0097] Subsequently, the dose-effect curve measurements of the test substances were repeated at least 10 times. Registered electrical activity patterns were characterized by 220 characteristics and their changes were statistically evaluated.

[0098] Next, an additional analysis was carried out through a pattern recognition analysis and through a comparison with the NeuroProof database to determine the relevant mechanisms involved in the induced changes of the frontal cortex activity pattern For each substance.

materials

[0099] Chemicals 5-fluoro-2'-deoxyuridine + uridine (FDU), and poly-D-lysine were obtained from Sigma-Aldrich Chemical GmbH (Steinheim, Taufkirchen, Germany). DNase I (of bovine pancreas), and laminin were purchased from Roche (Mannheim, Germany), fetal bovine serum from Biotech GmbH (Aidenbach, Germany), and PAA acutase (Germany). Horse serum and Dulbecco's modified essential medium (DMEM) were purchased from GIBCO BRL (Paisley, United Kingdom).

Neurochips of microelectrode groups

[0100] Microelectrode group neurochips (MEA neurochips) were provided by the Center for Network Neuroscience (CNNS) at the University of North Texas. These 5x5 cm2 glass chips have a central registration matrix with 64 passive electrodes and indium tin oxide conductors. The surface of the hydrophobic insulation material was activated by a brief pulse of butane flame through a stainless steel mask. In this way, cell binding is ensured is a confined adhesive region (5 mm diameter centered on the electrode group). The activated surface regions were coated with poly-D-lysine (25 μg / ml; 30-70kD) and laminin (16 μg / ml). Manufacturing techniques and culture methods have been previously described.

Cell culture

[0101] Frontal cortex tissue was collected from chr embryonic mice: NMRI on day 14 or 15. After anesthesia with ethyl ether, mice were sacrificed by cervical dislocation according to Act 4 of the Protection of Animals of Germany. Neural tissue was cultured including the use of DNAse I (8000 units / ml) and acutase (10 U / ml) for tissue dissociation. The tissue was enzymatically dissociated with acutase and mechanically with transfer pipettes. The cells were resuspended in 10/10 DMEM (10% horse serum and 10% fetal calf serum) at a density of 1.0 x 10 6 cells / ml, and 400 ml were grown on MEA surfaces. The cultures were incubated at 37 ° C in an atmosphere of 10% CO 2 until they were ready for use, which is normally four weeks to three months after cultivation. The culture media were filled three times per week with DMEM containing 10% horse serum. As in the tissue of origin, networks develop from a mixture of different types of neurons and postmitotic glial cells. Glial cells have important auxiliary functions for metabolism and for supplying neurons with ions and nutrients. Developing cocultures were treated with 5-fluoro-2’-deoxyuridine (25 μM) and uridine (63 μM) for 48 h to prevent further glial proliferation.

[0102] Cells that grew directly on neurochips appear as natural neural networks. These are composed of a mixture of neurons and glial cells comparable to the tissue of origin, while in the interaction with neurons, glial cells fulfill various functions of metabolism and transport. The neurons were electrically coupled to the neurochip electrodes, whereby the action potentials of the cells can be recorded and their amplitudes and the pattern of electrical activity can be evaluated.

[0103] The activity begins approximately three to four days in vitro in the form of random action potentials. Only after establishing a stable activity pattern after 4 weeks, neural networks are used in substance analysis. For this study, cultures between 26 and 29 days in vitro were used.

Multi-channel registration

10 [0104] For extracellular registration, MEA neurochips were placed in recording chambers with a constant sterilized bath and kept at 37 ° C. Registries were made in DMEM / 10% horse serum. The pH was maintained at 7.4 with a continuous flow stream of filtered and humidified air with 10% CO2. Groups of preamps were placed on either side of the recording chamber. Registration was performed with a multi-channel acquisition processor system, a 64-channel computer-controlled amplifier system (Plexon, Inc.,

15 Dallas, TX, United States) that provides amplification, filtration, programmable changes and digital signal processing of microelectrode signals. The total system gain was 10K with a sampling rate of 40 kHz. The signals routinely recorded by these neurochips are located in the range of 15-1800 mV.

[0105] The multi-channel signal acquisition system provided data on the action potentials of individual neurons. The identification and separation of action potentials was performed with an algorithm paired to a template in real time. This allowed the extracellular recording of action potentials of a maximum of 256 neurons simultaneously.

[0106] Action potentials, or spikes, were recorded in trains of action potentials and grouped into so-called bursts. Bursts were quantitatively described through direct analysis of action potentials using the NeuroEXplorer program (Plexon Inc., Dallas, TX, United States) and internal programs. Bursts were defined by the start and end of short action potentials. The maximum intervals of the action potentials that define the start of a burst were adjusted from 50 to 150 ms and the maximum intervals for

30 finish a burst of 100 to 300 ms.

Multiparameter data analysis

[0107] Analysis of the high content of network activity patterns provided a description

Multiparameter that characterizes the changes in four categories: general activity, burst structure, synchronicity and oscillatory behavior. Changes in the specific activity of the substance were quantified by the calculation for each phase of stable activity after the application of the substance of a total of 200 parameters of the train of action potentials that describe the activity for these four categories.

40 Statistical analysis

[0108] The results are expressed as the series average ± SEM. The absolute distributions of the parameters for normality were analyzed. The level of significance was evaluated after application of the compound using the paired Student t test. A significance between two substances or in relation to a

Content solvent (eg DMSO) using the unpaired Student t test. P <0.05 was considered statistically non-significant.

[0109] For direct comparability, all parameters for each experiment and each experimental treatment were normalized with respect to the corresponding values of the reference activity (native or after

50 of receiver blocking if applicable set to 100%).

[0110] For each experiment, the rate of change of action potentials as a function of concentration was adjusted to a sigmoidal dose-response curve of a multiphasic phase or sigmoidal phase provided by the equation:

60 which determines the values of the effective concentration that cause 10, 50, and 90% of the effect (EC10, EC50, and EC90) and of the slope (Hill coefficient nH; describes the slope of the curve: a high value corresponds to a significant decrease that could correspond to a functional neurotoxicity). In the case of the multiphase response due to several mechanisms of action, the term on the right is repeatedly added to the phases

65 additional.

Pattern Recognition and Classification

[0111] To clarify the mode of action of the test substance on the activity of cortical networks, these experiments were further analyzed using pattern recognition methods. For each phase of stable concentration activity, the 200 parameters of the action potential train were normalized by the native reference activity. These data records were computerized for test substances and reference substances.

[0112] Using a feature selection algorithm, based on the reference substances, the 40 most descriptive parameters for the 200 parameters of the action potential train were selected. Classifications of activity characteristics were calculated using various valuation methods based on the classification experiments and compared to their total correct predictions. In this way, the best results were obtained for a modified MDL algorithm (minimum description length). A set of preparation data was established with these 40 parameters of the action potential train in the form of data records of the reference substances. Next, an artificial neural network, a multilayer proactive network and a backpropagation algorithm without hidden units were prepared. Subsequently, the records of the respective data of the four substances were classified. A classification against 105 substances was carried out in the database.

Results:

[0113] In general, vicenin 2 has the effect of inducing a decrease in the activity of cortical networks with an EC50 at 2 pg / ml and a maximum decrease up to 80% of the native activity without affecting the structure of the burst , but to the oscillatory behavior of the network. These results are shown in Figure 6, which illustrates the concentration-dependent changes in cortical network activity. It could be seen that vicenin 2 influences neuroactivity. In a second stage, this activity was subsequently evaluated through a classification against positive controls.

Classifications

[0114] Classification against 105 substances using the multichannel electrophysiological record of vicenin 2 and the 105 substances identified several activities for vicenin 2.

Table 1 shows the summaries of the 10 highest classifications.

Olanzapine Serum Amisulpride Encephalin Sodium dodecyl sulfate Atropine methyl bromide Nicotine Indatraline Modafinil DPDPE

[0115] Table 1. Classification of vicenin 2 (AUC-V) against the NeuroProof database. A classification of the results of the classification is shown, which means that x-% of all data records of this substance were classified as the respective substance in the left column; DS corresponds to the relative general classification.

[0116] For example, it was possible to identify the sedative and anxiolytic activity of vicenin 2 by classification against olanzapine and amisulpride. Olanzapine is a serotonergic agent such as the 5-HT3 antagonist, the 5-HT3 partial agonist and the 5-HT4 agonist.

[0117] In addition, it was also possible to confirm the pain reduction activity of vicenin 2 by classification against enkephalin. Encephalins are endogenous ligands that bind to opioid receptors in the body that lead to antinociceptive activity.

[0118] Surprisingly, Vicenin 2 also showed a multichannel electrophysiological record comparable to the pattern of positive controls for eserine and nicotine. Eserin is a reversible cholinesterase inhibitor and nicotine acts as an acetylcholine agonist.

Results:

[0119] The prokinetic effect improves gastrointestinal mobility by increasing the frequency of contractions in the small intestine, but without changing its rhythm. This leads to relief of gastrointestinal symptoms, such as abdominal discomfort, swelling, constipation and other symptoms related to functional dyspepsia or irritated bowel syndrome. Surprisingly, the vicenin 2 compound has a prokinetic activity acting in two different ways. Firstly as a reversible cholinesterase inhibitor, and secondly as an acetylcholine agonist.

[0120] In summary, the Vicenin 2 compound has prokinetic effects through two different modes of action that probably help when there is an irregular contraction that leads to reduced GI mobility and GI symptoms. This effect has not been previously described for any flavonoid glycoside.

Summary

[0121] In summary, Vicenin 2 surprisingly demonstrated antispasmodic and prokinetic efficacy.

[0122] It was analyzed for its antispasmodic effect in an ex vivo animal study using isolated rat intestine, example 1. The antispasmodic effect with respect to the cholinergic system (acetylcholine) and with respect to a non-specific contraction mediated by Ba ++ was investigated. Vicenin 2 has antispasmodic activity, inhibiting neurotropic and musculotropic activity.

[0123] Neurotropic activity was also confirmed in an in vitro study analyzing the acute neuroactive effect of vicenin 1 on the neuronal activity of murine frontal cortex networks using multichannel electrophysiological records. The multichannel electrophysiological record of vicenin 2 showed a pattern comparable to the positive control of atropinmethyl bromide.

[0124] In addition, the prokinetic effect was observed based on two different modes of action. First, vicenin 2 showed a multichannel electrophysiological record comparable to the positive serine control pattern for reversible cholinesterase inhibition, and secondly, it showed a comparable pattern with nicotine, which acts as an acetylcholine agonist. Both modes of action increase the activity of the parasympathetic system and, consequently, lead to superior gastrointestinal activity.

[0125] The combination of antispasmodic and prokinetic effects lead to beneficial effects that aid in the health of the intestine.

References

[0126]

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 Irritable bowel syndrome, Gastroenterology, 60, 1, 2005

Four.

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5.

 The functional gastrointestinal disorder and the Rome III process, D.A. Drossmann, Gastroenterology, 130, 13771390, 2006

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 University of Maryland, Medical center, Medical reference for IBS www.umm.edu/altmed/articl/irritable-bowel000098.htm

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 Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer. Nagaprashantha LD, et al., Biochem Pharmacol, 7, 2011

8.

 Vicenin-2, a potential anti-inflammatory constituent of Urtica circularis, Marrassini C, et al, J Nat Prod. 24; 74 (6): 1503-7, 2011

9.

 Comparative studies on anxiolytic activities and flavonoid compositions of Passiflora edulis ’edulis’ and Passiflora edulis ’flavicarpa’, Li H, et al, J Ethnopharmacol, 16; 133 (3): 1085-90, 2011

10.

 Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis. Gorzalczany S, et al, J Ethnopharmacol.,; 134 (3): 733-8, 2011

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 Neuropharmacological activity of the pericarp of Passiflora edulis flavicarpa degener: putative involvement of Cglycosylflavonoids, Sena LM, et al., Exp Biol Med (Maywood), (8): 967-75, 2009

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 The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis, the local production of 5-hydroxytryptamine and its release in relation to intraluminal pressure and propulsive activity. Bülbring, E., et al, J. Physiol. (Lond) 140, 381-407, 1958

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Claims (11)

one.

 Composition comprising vicenin 2 as an antispasmodic and / or prokinetic agent for use in i) preventing or improving irritable bowel syndrome (IBS), ii) having a beneficial physiological effect to maintain, prevent and / or improve functional dyspepsia (FD) , iii) reduce or balance digestive disorders, iv) reduce swelling, v) improve diarrhea or vi) reduce visceral hypersensitivity and / or abdominal pain.

2.

 Use of a composition comprising vicenin 2 to maintain a healthy bowel, maintain normal digestion, improve bowel regularity, aid in healthy bowel mobility, bowel movement and / or a frequency of bowel movements, consistency and / or form of healthy bowel movements and / or improve bowel function and / or induce antispasmodic and / or prokinetic activity.

3.

 Composition for use according to claim 1, or use according to claim 2, wherein the composition comprises or derives from a plant preparation comprising the active ingredient or in which the vicenin 2 is an isolated vicenin 2 obtained by isolation or chemical synthesis

Four.

 Composition for use according to claim 3, or use according to claim 3, wherein the plant preparation has been enriched in the active ingredient.

5.

 Composition for use according to claim 4, or use according to claim 4, wherein the plant preparation is selected from the group consisting of Perilla, Urtica, Passiflora, Camellia, Cayaponia, Colocasia, Desmodium, Hordeum, Origanum, Ocimum, Jatropha, Parkinsonia, Peperomia, Piheranthos, Centaurea, Indigo, Bomb, Lychnophera, Asplenium, Chinotto, Citrus, Viola, Trigonella, rosemary, mint, thyme, basil, sage, oregano, lavender and other species belonging to Lamiaceae, Labiatae and Urticaceae , Rosales or Malpighiales and in which, preferably, the vegetable preparation is a leaf preparation, a fruit preparation, a seed preparation, a stalk preparation, a flower preparation, a cocoon preparation, a root preparation or A mixture of different parts of the plant.

6.

 Composition for use according to claim 1 or 3 to 5, or use according to any of claims 2 to 5, which is comprised in a food product, a dietary supplement or medicament.

7.

 Composition for use according to claim 1 or 3 to 6, or use according to any of claims 2 to 6, wherein the concentration of the active ingredient is 0.1 μg to 500 μg, preferably 2.5 μg to 50 μg and most preferably from 5 μg to 15 μg.

8.

 Composition for use, according to claim 1 or 3 to 7, or use, according to any of claims 2 to 7, wherein the preparation is a plant extract, most preferably a liquid or powder extract obtained by extraction.

9.

 Composition for use, according to claim 1 or 3 to 8, or use, according to any of claims 2 to 8, comprising an additional agent capable of improving bowel health.

10.

 Composition for use according to claim 9, or use according to claim 9, wherein the agent is a prebiotic agent, a probiotic agent, a lipid, a loading agent, a medicament, an antispasmodic agent, a prokinetic agent or an anti-inflammatory agent

eleven.

 Composition for use according to claim 10, or use according to claim 10, wherein the medicament is an additional antispasmodic agent, a tricyclic antidepressant, a cholecystokinin-1 antagonist, a serotonergic agent, a benzodiazepine or the like, an antagonist of neuroquinine, a guanylate cyclase C agonist, a C1-C2 channel activator, a Cl secretion blocker, a GLP1 analogue, an κ-opioid agonist, an antacid, a sodium phosphate, an inhibitor of reuptake of NA, an analogue of omeprazole, glucocorticoid or an antibiotic.